Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Tổng hợp, hoạt động kháng khuẩn và chống phát triển tế bào, phân tử docking, và nghiên cứu tính toán của các hợp chất dị vòng mới
Tóm tắt
Chúng tôi đã nghiên cứu phản ứng của enaminone 3 với một số nucleophile nitrogen để tạo ra các dẫn xuất pyrazole 4, isoxazole 5 và pyrimidine 6 tương ứng, cũng như tính phản ứng của enaminone 3 với các amin dị vòng để tạo ra các dẫn xuất pyrrolo[1,2-a]pyrimidine 9a, imidazo[1,2-a]pyrimidine 9b, phenylpyrrolo[1,2-a]pyrimidine 9c và benzo[4,5]imidazo[1,2-a]pyrimidine 11. Thêm vào đó, phản ứng azo-coupling điện tích của enaminone 3 với các muối diazonium thơm trong pyridine đã tạo ra các hydrazine trung gian 13a–d, mà sau đó vòng hóa thành các dẫn xuất pyrazolo[5,1-c][1,2,4]triazine 14a–d. Hơn nữa, sự cộng hợp của (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (3) với các dẫn xuất hydrazonoyl chloride 15a,b đã cho ra các dẫn xuất pyrazole mới 17a,b. Hầu hết các hợp chất dị vòng được tổng hợp đều thể hiện hoạt tính kháng khuẩn và hoạt tính chống ung thư in vitro (trên dòng tế bào HepG2 và MCF-7). Hơn nữa, việc docking phân tử của hợp chất hiệu quả nhất, tức là 7-(4-fluorophenyl)pyrazolo[5,1-c][1,2,4]triazin-3-yl)(2-hydroxyphenyl)methanone (14c), đã được nghiên cứu đối với (PDB ID: 3t88), (PDB ID: 2wje), (PDB ID: 4ynt), và (PDB ID: 1tgh) để khảo sát hoạt tính kháng khuẩn của nó khi gắn vào các protein khác nhau với chiều dài liên kết ngắn. Hợp chất 14a được docking với (PDB ID: 4hdq) và (PDB ID: 3pxe) với năng lượng ái lực lần lượt là −9.946 và −10.55 kcal/mol, với dẫn xuất pyrazolo[5,1-c][1,2,4]triazine tham gia vào các túi của protein. Hơn nữa, các nghiên cứu lý thuyết và thực nghiệm của các hợp chất 14a,c phù hợp với dữ liệu phổ thu được ở mức HF/6-31G(d) và DFT/B3LYP/6-31G(d).
Từ khóa
#tổng hợp #hoạt động kháng khuẩn #hoạt tính chống phát triển tế bào #phân tử docking #nghiên cứu tính toán #hợp chất dị vòngTài liệu tham khảo
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